The aim of this pilot project component of the P50 application on Center for Alcohol Research in Epigenetics (CARE) is to provide a flexible means to explore new ideas and directions in alcohol research and also to attract new investigators (in the early stages of their careers or already established) that are well suited for the objectives of the center. During the first two years, we have proposed to explore epigenetic changes in mitochondria (Pilot project 1: Dr. Hari Manev) and microglial cells (Pilot project 2: Dr. Douglas Feinstein) during alcoholism. These areas were considered since they play an important role in the regulation of brain physiology during alcoholism and they fit nicely with the epigenetic theme of CARE. Linking translational research with basic science research is another important area within the alcohol research field. The functional effects of neuroadaptation of the human brain secondary to long-term alcohol consumption are largely unknown. Disruption of cortico-limbic circuitry may exert its most detrimental effects on the capacity to effectively regulate negative affect resulting in exaggerated anxiety. A second set of pilot projects will be selected for the 3rd and 4th years of CARE that will investigate the epigenetics of human and animal models, blood cells, and neuroimaging studies during alcoholism. Several classes of functional noncoding RNAs, including miRNAs, have been implicated in the regulation of gene expression and synaptic plasticity. Recent findings suggest a complex interaction occurs between miRNAs and epigenetic machinery. In addition, gender differences in the development of alcoholism have been demonstrated in the field. A third set of pilot projects will be announced and selected in these areas during the 5th year of CARE funding. We propose to complete six pilot projects during the period of CARE funding. The administrative core will provide leadership, overall management and oversight of these pilot projects. Dr. Subhash Pandey will serve as PI and Dr. Alessandro Guidotti will serve as co-investigator of this component. The pilot projects will be announced and applications will be reviewed by the Scientific Advisory Committee members for thematic fitness, innovation and significance to CARE's overall objectives.